Genetic Variant TCP1:p.Asp547Glu (chr6-159779075-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030752.3(TCP1):c.1641T>A(p.Asp547Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D547N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

TCP1
NM_030752.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0450

Publications

0 publications found

Variant links:

Genes affected

TCP1 (HGNC:11655): (t-complex 1) The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Alternate transcriptional splice variants of this gene, encoding different isoforms, have been characterized. In addition, three pseudogenes that appear to be derived from this gene have been found. [provided by RefSeq, Jun 2010]

TCP1 links:

ACAT2 (HGNC:94): (acetyl-CoA acetyltransferase 2) The product of this gene is an enzyme involved in lipid metabolism, and it encodes cytosolic acetoacetyl-CoA thiolase. This gene shows complementary overlapping with the 3-prime region of the TCP1 gene in both mouse and human. These genes are encoded on opposite strands of DNA, as well as in opposite transcriptional orientation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

ACAT2 Gene-Disease associations (from GenCC):

acetyl-CoA acetyltransferase-2 deficiency
Inheritance: AR, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen

ACAT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07059413).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030752.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCP1	NM_030752.3	MANE Select	c.1641T>A	p.Asp547Glu	missense	Exon 12 of 12	NP_110379.2	P17987
ACAT2	NM_005891.3	MANE Select	c.*246A>T		3_prime_UTR	Exon 9 of 9	NP_005882.2	Q9BWD1-1
TCP1	NM_001008897.2		c.1176T>A	p.Asp392Glu	missense	Exon 11 of 11	NP_001008897.1	E7EQR6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCP1	ENST00000321394.12	TSL:1 MANE Select	c.1641T>A	p.Asp547Glu	missense	Exon 12 of 12	ENSP00000317334.7	P17987
ACAT2	ENST00000367048.5	TSL:1 MANE Select	c.*246A>T		3_prime_UTR	Exon 9 of 9	ENSP00000356015.4	Q9BWD1-1
TCP1	ENST00000934596.1		c.1626T>A	p.Asp542Glu	missense	Exon 12 of 12	ENSP00000604655.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.82

M_CAP

Benign

0.010

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

0.045

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

REVEL

Benign

0.18

Sift

Benign

0.28

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.12

MutPred

0.21

Gain of solvent accessibility (P = 0.1014)

MVP

0.57

MPC

0.45

ClinPred

0.34

GERP RS

0.98

Varity_R

0.089

gMVP

0.76

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over